Discussion

Ferroptosis is a form of non-apoptotic cell death described in mammalian cells, characterized by iron-dependent lipid peroxidation and glutathione peroxidase 4 (GPx 4) is its main regulator. Trypanosoma brucei possess three tryparedoxin peroxidases (Px I-III), related to GPx 4. Flow cytometry analysis of procyclic Px I-III KO cells using MitoSOX revealed reactive oxygen species production in the mitochondrion that was prevented by the iron chelator deferoxamine. Following 10-nonyl acridine orange fluorescence indicated cardiolipin peroxidation. As superoxide anions induce the formation of labile iron, the effect of overexpressing mitochondrial superoxide dismutase on Px I-III KO cells is currently investigated, as are different ferroptosis inhibitors. This work will shed light on the mechanism of iron-mediated cell death in T. brucei.